{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhang Z"],"funding":["ERC IMI","Temasek Trust","NIHR Imperial Biomedical Research Centre","H2020","UKRI guarantee funding for Horizon Europe MSCA Postdoctoral Fellowships","Boehringer Ingelheim Ltd","Royal Society","UKRI MRC Research Grant","UKRI Future Leaders Fellowship","Swiss National Science Foundation","POLG Foundation","NVIDIA Academic Hardware Grant Program","University of Bergen Meltzers Høyskolefonds","Medical Research Council","TFS Research Grants","Gerda Meyer Nyquist Legat"],"pagination":["e17721"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12822396"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13(4)"],"pubmed_abstract":["Mitochondrial dysfunction and impaired neurogenesis are central to mitochondrial DNA polymerase (POLG)-related disorders, yet therapeutic options remain limited. Here, patient-derived induced pluripotent stem cell (iPSC)-based cortical organoids are used to model POLG-associated neurodegeneration and assess the therapeutic potential of metformin. Single-cell RNA-seq reveals distinct vulnerabilities in dopaminergic, glutamatergic, and GABAergic neuronal subtypes, with dopaminergic neurons exhibiting the most severe loss and mitochondrial transcriptomic deficits. Metformin treatment (250 µm, 2 months) significantly restores neuronal identity, subtype-specific gene expression, and mitochondrial function. Functional assays demonstrate improved mitochondrial membrane potential (TMRE), increased"],"journal":["Advanced science (Weinheim, Baden-Wurttemberg, Germany)"],"pubmed_title":["Metformin Restores Mitochondrial Function and Neurogenesis in POLG Patient-Derived Brain Organoids."],"pmcid":["PMC12822396"],"funding_grant_id":["952172","103816102","RDA01","IEC∖NSFC∖211235","103517133","MR/V023799/1","101005122","MR/U506710/1","220785","MC/PC/21013","104291","EP/Z002206/1"],"pubmed_authors":["Deng S","Yang G","Yangzom T","Lu N","Zhang Z","Xiao X","Liang KX"],"additional_accession":[]},"is_claimable":false,"name":"Metformin Restores Mitochondrial Function and Neurogenesis in POLG Patient-Derived Brain Organoids.","description":"Mitochondrial dysfunction and impaired neurogenesis are central to mitochondrial DNA polymerase (POLG)-related disorders, yet therapeutic options remain limited. Here, patient-derived induced pluripotent stem cell (iPSC)-based cortical organoids are used to model POLG-associated neurodegeneration and assess the therapeutic potential of metformin. Single-cell RNA-seq reveals distinct vulnerabilities in dopaminergic, glutamatergic, and GABAergic neuronal subtypes, with dopaminergic neurons exhibiting the most severe loss and mitochondrial transcriptomic deficits. Metformin treatment (250 µm, 2 months) significantly restores neuronal identity, subtype-specific gene expression, and mitochondrial function. Functional assays demonstrate improved mitochondrial membrane potential (TMRE), increased","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026 Jan","modification":"2026-06-06T19:46:43.03Z","creation":"2026-06-04T03:11:19.373Z"},"accession":"S-EPMC12822396","cross_references":{"pubmed":["41355579"],"doi":["10.1002/advs.202417721"]}}